The long-range objective of this study is to gain better insight into the correlation between the hepatic ultrastructure and function regarding bile secretion and stasis. Efforts will be focused on understanding the functional significance of the following structures: 1) the bile canaliculus, 2) the lateral and sinusoidal surfaces of the hepatocytes, 3) the junctional complexes, 4) the cytoskeletal system, 5) the Golgi apparatus and transport vesicles, 6) the bile duct, and 7) the hepatic acinus with respect to: 1) acute cholestasis and choleresis induced by bile acids, 2) inhibition of the bile acid-independent bile secretion by such agents as scillaren (a cardiac glycoside known to inhibit Na ion, K ion-ATPase), indocyanain green, or rose Bengal, 3) bile acid-independent choleresis by SC-2644, 4) localization of Na ion, K ion-ATPase, 5) ultrastructural basis for paracellular fluid transport, 6) ultrastructural basis for transcellular fluid transport, and 7) localization of bile acids in the hepatic tissue. These studies will be carried out using whole animals, e.g., rats and rabbits, and the isolated perfused liver.